1. Technical Field of the Invention
The present invention relates to a process for realizing microchannels in an integrated structure. More specifically, the invention relates to a process for realizing microchannels buried in an integrated structure comprising a monocrystalline silicon substrate.
2. Description of Related Art
Typical procedures for analyzing biological materials, such as nucleic acid, involve a variety of operations starting from raw material. These operations may include various degrees of cell purification, lysis, amplification or purification, and analysis of the resulting amplification or purification product.
As an example, in DNA-based blood tests the samples are often purified by filtration, centrifugation or by electrophoresis so as to eliminate all the non-nucleated cells. Then, the remaining white blood cells are lysed using chemical, thermal or biochemical means in order to liberate the DNA to be analyzed. Next, the DNA is denatured by thermal, biochemical or chemical processes and amplified by an amplification reaction, such as PCR (polymerase chain reaction), LCR (ligase chain reaction), SDA (strand displacement amplification), TMA (transcription-mediated amplification), RCA (rolling circle amplification), and the like. The amplification step allows the operator to avoid purification of the DNA being studied because the amplified product greatly exceeds the starting DNA in the sample.
The procedures are similar if RNA is to be analyzed, but more emphasis is placed on purification or other means to protect the labile RNA molecule. RNA is usually copied into DNA (cDNA) and then the analysis proceeds as described for DNA.
Finally, the amplification product undergoes some type of analysis, usually based on sequence or size or some combination thereof. In an analysis by hybridization, for example, the amplified DNA is passed over a plurality of detectors made up of individual oligonucleotide detector “probes” that are anchored, for example, on electrodes. If the amplified DNA strands are complementary to the probes, stable bonds will be formed between them and the hybridized detectors can be read by observation by a wide variety of means, including optical, electrical, magnetic, mechanical or thermal means.
Other biological molecules are analyzed in a similar way, but typically molecule purification is substituted for amplification and detection methods vary according to the molecule being detected. For example, a common diagnostic involves the detection of a specific protein by binding to its antibody or by a specific enzymatic reaction. Lipids, carbohydrates, drugs and small molecules from biological fluids are processed in similar ways. However, we have simplified the discussion herein by focusing on nucleic acid analysis, in particular DNA amplification, as an example of a biological molecule that can be analyzed using the devices of the invention.
The steps of nucleic acid analysis described above are currently performed using different devices, each of which presides over one aspect of the process. The use of separate devices increases cost and decreases the efficiency of sample processing because transfer time between devices is required, larger samples are required to accommodate sample loss and instrument size, and because qualified operators are required to avoid contamination problems. For these reasons an integrated microreactor would be preferred.
For performing treatment of fluids, integrated microreactors of semiconductor material are already known. Microchannel arrays are widely used in different systems such as medical systems for fluid administration, devices for biological use for manufacturing miniaturized microreactors, in electrophoresis processes, in DNA chip and other array applications, in integrated fuel cells, ink jet printers, and the like. Microchannels are used also, for example, for the refrigeration of devices located above microchannels.
One application of interest is the use of microchannels to make a miniaturized microreactor for diagnostic uses (see especially, U.S. Ser. No. 10/663,268 filed Sep. 16, 2003 and references cited therein, each which incorporated by reference in their entirety). A number of such devices are described for the amplification of nucleic acid, such as DNA or RNA, or for other biological tests, such as immunological detection of antigens in a biological sample. The microreactor can be combined with one or more integrated sample pretreatment chamber, micropump, heater, and also with integrated sample analysis features, such as an array of nucleic acid or antibody detectors. Such devices are described in more detail in U.S. Ser. No. 10/663,268, and related patents or applications.
However, complex procedures are traditionally required in order to form a microchannel system. In particular, conventional processes for forming embedded microchannels require so-called wafer bonding or opening structures from the backside of the wafer back.
A process for forming microchannels is described for example in the U.S. Pat. No. 6,376,291 granted on Apr. 23, 2002. In particular, this document describes a process for forming in a monocrystalline silicon body an etching-aid region for the monocrystalline silicon wherein a nucleus region is provided, surrounded by a protective structure and having a port extending along the whole etching-aid region.
According to the '291 patent, a polycrystalline layer is grown above the port in order to form a cavity completely embedded in the resulting wafer. Although advantageous from many aspects, the process described by the '291 patent is rather complex and it does not allow a completely crystalline final microstructure to be obtained.
The technical problem underlying the present invention is to provide a process for forming microchannels, having such structural and functional characteristics as to overcome the limits and drawbacks still affecting the processes according to the prior art.